The isolation of fermentation derived secondary metabolites is often required for the synthesis of semi-synthetic anti-infective drugs. Typically, secondary metabolites have a molecular weight range of 300-2000 kD and potentially can be thermally labile. Single stage distillation is widely used during multi-step organic solvent-based processes in order to concentrate product streams, switch solvents for the next processing step or recover solvent for subsequent reuse. However, this form of distillation is not very efficient when processing with high boiling solvents such as isobutyl alcohol or solvent switching to a lower boiling solvent. It also does not provide any purification as typical fermentation impurities are nonvolatile.

Solvent resistant nanofiltration (SRNF) provides a novel alternative to distillation for the concentration and solvent switch of an active pharmaceutical intermediate. SRNF provides the potential advantages of increased efficiency, purification and selective solvent removal. This paper will present a comparison of a distillation based process versus a nanofiltration process, in terms of yield, purity, and productivity (kg/hr). The effect of molecular weight cut-off (MWCO), pressure, membrane loading, and diavolumes on the yield and purity of the product for two steps will be presented. SRNF was used to replace distillation for the initial concentration of an isobutyl alcohol whole broth extract. A 12 wt% increase in purity was observed vs. distillation based process - a purity increase which was carried through the subsequent isolation. A second distillation step of a mixed solvent composition (78% IPAc, 10% IBA, 7% MeOH & 5% water) was also replaced with SRNF. The concentration and diafiltration of the isopropyl acetate extract provided a clearance of IBA to the target specification of < 1% which increased the purity of the downstream precipitation by 10%. Overall both NF steps increased the productivity by 10 fold.